PROJECT: SUMMARY The prevalence of both obesity and kidney stones is increasing. Since calcium oxalate is the most common type of stone, it can be inferred that the prevalence of such calculi is also increasing. There is also evidence that obese individuals excrete more urinary oxalate, a risk factor for the development of calcium oxalate stones. Since obesity is a risk factor for kidney stones, and the prevalence of both conditions is high in Alabama, the local environment is ideally suited to conduct research to determine the reasons for these relationships. In this project we plan to address the hypothesis that obesity is associated with increased endogenous oxalate synthesis. We will merge the skill sets and knowledge present on the UAB campus in the Centers of Excellence in Obesity and Diabetes research with those in the Urology Kidney Stone Research Laboratory to address this hypothesis. We propose to form a Center for research on Obesity and Oxalate Kidney Stones (COOKS) to facilitate these collaborative investigations. We have developed 2 specific aims. In Specific Aim 1, we will employ a mouse model of diet-induced obesity to assess for this relationship which includes a novel approach, the utilization of 13C oxalate precursors, to measure endogenous oxalate synthesis. Endogenous oxalate synthesis primarily occurs in the liver and we will assess for perturbations in hepatic enzyme activities that promote endogenous oxalate synthesis. The impact of body fat content will also be measured. In Specific Aim 2, we will phenotype non-obese and obese non-kidney stone forming adults using controlled low oxalate diets to estimate endogenous oxalate synthesis. Body fat content and composition and insulin sensitivity will be measured in the Nutrition and Obesity Research Center (NORC) where one of the Associate Directors of the proposed center is also director of 2 NORC cores. We have conducted preliminary experiments in mice and humans which suggest that there are strong relationships between obesity and endogenous oxalate synthesis. The amalgamation of expertise in this Center should be a pathway for strong future collaborative research leading to a competitive R01 or Program Project Grant submission.